Long-term clinical follow-up of venous thromboembolism (VTE) can be complicated by excess morbidity and mortality. The use of genetic testing for the CYP2C9 and VKORC1 genes in order to guide warfarin dosing for patients with VTE holds significant promise potentially to reduce the incidence of over-and under anticoagulation. However, due to uncertainties regarding this new technology, it is unclear whether the genetic testing will be cost-effective given the increased cost of the intervention. Objective: This study proposes using a simulation model of the natural history of VTE to determine the cost-effectiveness of genetic testing for CYP2C9 and VKORC1 genes to guide long-term use of warfarin anticoagulation from the societal perspective. Methodology: A decision analysis using discrete event simulation will be developed to construct an economic model depicting the health states of a cohort of patients as the disease evolves over time. Associated costs and quality of life traits (utilities) of the complications will be captured. Data will be extrapolated with the criteria including patient age >18 years, confirmed clinical diagnosis of deep venous thrombosis or pulmonary embolism, warfarin therapy prescribed for at least 6 months, and an indication for target INR between 2 to 3. Input data will be obtained from the literature, HCUP-NIS, HCUP-SEDD, and the Medicare Reimbursement Schedule database. Sensitivity analysis on all parameters will be performed to account for uncertainly variables in the model. Main and Secondary Outcomes: Cost-effectiveness, measured in dollars per quality adjusted life years gained ($/QALY) will be calculated;and the incremental cost effectiveness ratio will be measured. PUBLIC HEALTH RELEVANCE: Venous thromboembolism (VTE) is a complicated condition faced by an increasing number of patients and is estimated at an incidence of 7 per 10000 personyears among community residents. Warfarin is the drug of choice for long-term anticoagulation therapy for the treatment of acute VTE episode and the prevention of VTE recurrences. However, despite the close monitoring to guide warfarin dosing for diagnosed patients, overall treatment management still poses many serious challenges and uncertainties (e.g. healthcare cost, outcome of warfarin use) in the long term clinical course of the disease. Due to warfarin's narrow therapeutic index and wide inter-individual variability in patient response and intensity of the treatment, the management of warfarin therapy may increase the risk of bleeding (e.g. hemorrhagic stroke, death) or recurrences of VTE (e.g. ischemic stroke). Therefore, prior to warfarin administration, it has been proposed to conduct a genetic test for the VKORC1 and CYP2C9 genes to identify those genotypes associated with high International Normalize Ratio (INR) and presumably decrease bleeding to help decrease the risk-to-benefit-ratio, and optimize patients'drug therapy while improving their outcomes and costs. The current study is proposed to assess the cost-effectiveness of genetic testing for the identified genes.